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Chapter 2The Pretravel Consultation

General Recommendations for Vaccination & Immunoprophylaxis

Andrew T. Kroger, Raymond A. Strikas

Recommendations for the use of vaccines and other biologic products (such as immune globulin [IG] products) in the United States are developed by the Advisory Committee on Immunization Practices (ACIP) and are harmonized with ACIP liaison organizations including the American Academy of Pediatrics, the American Academy of Family Physicians, the American College of Physicians, the American College of Obstetricians and Gynecologists, and others. Recommendations voted on by the ACIP are reviewed by the CDC director and, if adopted, become official recommendations of the Department of Health and Human Services/CDC upon publication in CDC’s Morbidity and Mortality Weekly Report (MMWR). ACIP recommendations are based on scientific evidence of benefits (disease immunity) and risks (vaccine adverse reactions) and, where few or no data are available, on expert opinion. Recommendations include information on general immunization issues and the use of specific vaccines. Box 2-01 provides more information about ACIP. This section is based primarily on the ACIP General Recommendations on Immunization.

Evaluation of people before travel should include a review and provision of routine vaccines recommended based on age and other individual characteristics. Additionally, some routine vaccines are recommended at earlier ages for international travelers. For example, MMR (measles-mumps-rubella) vaccine is recommended for infants aged 6–11 months who travel abroad to protect them from measles. Recommendations for specific vaccines related to travel will depend on itinerary, duration of travel, and host factors. Vaccinations against diphtheria, tetanus, pertussis, measles, mumps, rubella, varicella, poliomyelitis, hepatitis A, hepatitis B, Haemophilus influenzae type b (Hib), rotavirus, human papillomavirus (HPV), and pneumococcal and meningococcal invasive disease are routinely administered in the United States, usually in childhood or adolescence. Influenza vaccine is routinely recommended for all people aged ≥6 months, each year. A dose of herpes zoster (shingles) vaccine is recommended for adults aged ≥60 years. If a person does not have a history of adequate protection against these diseases, immunizations appropriate to age and previous immunization status should be obtained, whether or not international travel is planned. A visit to a clinician for travel-related immunizations should be seen as an opportunity to bring an incompletely vaccinated person up-to-date on his or her routine vaccinations.

Both the child and adolescent vaccination schedules, and an adult vaccination schedule, are published annually. Clinicians should obtain the most current schedules from the CDC Vaccines and Immunization website (www.cdc.gov/vaccines/schedules). The text and many tables of this publication present recommendations for the use, number of doses, dose intervals, adverse reactions, precautions, and contraindications for vaccines and toxoids that may be indicated for travelers. Recommendations for travelers are not always the same as routine recommendations. For instance, most adults born after 1956 are recommended to receive 1 dose of MMR vaccine; however, international travelers of this age are recommended to receive 2 doses. For specific vaccines and toxoids, additional details on background, adverse reactions, precautions, and contraindications, refer to the respective ACIP recommendations (www.cdc.gov/vaccines/acip/index.html).

Box 2-01. The Advisory Committee on Immunization Practices (ACIP)

In 1964, the Department of Health, Education, and Welfare chartered the Advisory Committee on Immunization Practices (ACIP) to provide guidance to CDC for making immunization policy. Guidance includes scheduling of vaccine doses, specific risk groups for whom vaccination is recommended, and vaccine contraindications and precautions.

ACIP is composed of 15 voting members selected by the Secretary of Health and Human Services. The ACIP chair, a consumer representative, and 13 members are balanced among various sectors, including academic immunology, medicine, and public health. In addition to the 15 voting members, the committee includes 8 ex officio members representing federal agencies and 35 nonvoting representatives of liaison organizations with broad responsibilities for vaccine development, administration of vaccines to various segments of the population, and operation of immunization programs. ACIP is subdivided into 4 permanent workgroups that address child/adolescent immunization schedules, adult immunization schedules, influenza vaccine, and general immunization issues. In addition to the 4 permanent workgroups, additional workgroups focus on particular vaccines. Input into the development of immunization schedules is shared with professional organizations, including the American Academy of Pediatrics, American College of Physicians, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and American College of Nurse-Midwives.

ACIP workgroups are led by a member of ACIP who works in close collaboration with a CDC workgroup lead staff member. Members of the vaccine pharmaceutical industry may not serve as workgroup members. The workgroup develops consensus on various policy points, then the CDC workgroup lead writes specific content for presentation to the ACIP at large. When it is difficult to achieve consensus, options with plans are developed and presented to the ACIP at large for a vote.

ACIP holds 3 public meetings a year during which the various workgroups present content that has been developed and is ready for discussion or voting. Sometimes ACIP members are involved in academic vaccine research supported by the pharmaceutical industry. These members must state these conflicts and must recuse themselves from votes regarding vaccines manufactured by companies from which they receive support. The result of various discussions and votes is an ACIP document published in CDC’s Morbidity and Mortality Weekly Report (www.cdc.gov/mmwr), representing the official policy of the Department of Health and Human Services.

SPACING OF IMMUNOBIOLOGICS

Simultaneous Administration

With some exceptions (such as PCV13 and PPSV23, as well as PCV13 and MenACWY-D [Menactra]), all commonly used vaccines can safely and effectively be given simultaneously (on the same day) at separate sites without impairing antibody responses or increasing rates of adverse reactions. This knowledge is particularly helpful for international travelers, for whom exposure to several infectious diseases might be imminent. Simultaneous administration of all indicated vaccines is encouraged for people who are the recommended age to receive these vaccines and for whom no contraindications exist. If not administered on the same day, an inactivated vaccine may be given at any time before or after a different inactivated vaccine or a live-virus vaccine.

The immune response to an injected or intranasal live-virus vaccine (such as MMR, varicella, yellow fever, or live attenuated influenza vaccines) might be impaired if administered within 28 days of another live-virus vaccine (within 30 days for yellow fever vaccine). Whenever possible, injected live-virus vaccines administered on different days should be given ≥28 days apart (≥30 days for yellow fever vaccine). If 2 injected or intranasal live-virus vaccines are not administered on the same day but <28 days apart (<30 days for yellow fever vaccine), the second vaccine should be repeated in ≥28 days (≥30 days for yellow fever vaccine).

Measles and other live-virus vaccines may interfere with the response to tuberculin skin testing and the interferon-γ release assay. Tuberculin testing, if otherwise indicated, can be done either on the day that live-virus vaccines are administered or 4–6 weeks later. Tuberculin skin testing is not a prerequisite for administration of any vaccine. Oral typhoid vaccine, a live attenuated bacterial vaccine, has not been associated with suppressing the response to tuberculosis testing.

Missed Doses and Boosters

All vaccines require a primary dose or series to ensure immunity, and some require periodic repeat, or booster, doses to maintain immunity. Occasionally, the demand for a vaccine may exceed its supply, and providers may have difficulty obtaining vaccines. Information on vaccine shortages and recommendations can be found on the CDC Vaccines and Immunization website at www.cdc.gov/vaccines/hcp/clinical-resources/shortages.html.

In some cases, a scheduled dose of vaccine may not be given on time. If this occurs, the dose should be given at the next visit. However, travelers may forget to return to complete a series or for a booster at the specified time. Available data indicate that intervals between doses longer than those routinely recommended do not affect seroconversion rate or titer when the schedule is completed. Consequently, it is not necessary to restart the series or add doses of any vaccine because of an extended interval between doses. There are some exceptions to this rule. Some experts recommend repeating the series of oral typhoid vaccine if the 4-dose series is extended to more than 3 weeks. If an extended interval passes between doses of the preexposure rabies vaccine series, immune status should be assessed by serologic testing 7–14 days after the final dose in the series.

Antibody-Containing Blood Products

Antibody-containing blood products from the United States, such as immune globulin (IG) products, do not interfere with the immune response to yellow fever vaccine and are not believed to interfere with the response to live typhoid, live attenuated influenza, rotavirus, or zoster vaccines. When MMR and varicella vaccines are given shortly before, simultaneously with, or after an antibody-containing blood product, response to the vaccine can be diminished. The duration of inhibition of MMR and varicella vaccines is related to the dose of IG in the product. MMR and varicella vaccines either should be administered ≥2 weeks before receipt of a blood product or should be delayed 3–11 months after receipt of the blood product, depending on the dose and type of blood product (Table 2-04).

IG administration may become necessary for another indication after MMR or varicella vaccines have been given. In such a situation, the IG may interfere with the immune response to the MMR or varicella vaccines. Vaccine virus replication and stimulation of immunity usually occur 2–3 weeks after vaccination. If the interval between administration of one of these vaccines and the subsequent administration of an IG preparation is ≥14 days, the vaccine need not be readministered. If the interval is <14 days, the vaccine should be readministered after the interval shown in Table 2-04, unless serologic testing indicates that antibodies have been produced. Such testing should be performed after the interval shown in Table 2-04, to avoid detecting antibodies from the IG preparation.

If administration of IG becomes necessary, MMR or varicella vaccines can be administered simultaneously with IG, with the recognition that vaccine-induced immunity can be compromised. The vaccine should be administered at a body site different from that chosen for the IG injection. Vaccination should be repeated after the interval noted in Table 2-4, unless serologic testing indicates antibodies have been produced.

When IG is given with the first dose of hepatitis A vaccine, the proportion of recipients who develop a protective level of antibody is not affected, but antibody concentrations are lower. Because the final concentrations of antibody are many times higher than those considered protective, this reduced immunogenicity is not expected to be clinically relevant. However, the effect of reduced antibody concentrations on long-term protection is unknown.

IG preparations interact minimally with other inactivated vaccines and toxoids. Other inactivated vaccines may be given simultaneously, or at any time interval before or after an antibody-containing blood product is used. However, such vaccines should be administered at different sites from the IG.

Abbreviations: IG, immune globulin; IM, intramuscular; IV, intravenous.1Adapted from Table 5, CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61. Updated with information from CDC. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Jun 14; 62(RR-04):1–34. This table is not intended for determining the correct indications and dosage for the use of IG preparations. Unvaccinated people may not be fully protected against measles during the entire recommended interval, and additional doses of IG or measles vaccine may be indicated after measles exposure. Concentrations of measles antibody in an IG preparation can vary by manufacturer’s lot. For example, more than a 4-fold variation in the amount of measles antibody titers has been demonstrated in different IG preparations. Rates of antibody clearance after receipt of an IG preparation can also vary. Recommended intervals are extrapolated from an estimated half-life of 30 days for passively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months after a dose of 80 mg IgG/kg. Does not include zoster vaccine. Zoster vaccine may be given with antibody-containing products.2Assumes a serum IgG concentration of 16 mg/mL.3Recommendation adapted from Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207.4If varicella zoster immune globulin is not available, IVIG can be used. The recommendation for use of IVIG is based on best judgment of experts and is supported by reports comparing varicella IgG titers measured in both IVIG and varicella zoster immune globulin preparations and patients given IVIG and varicella zoster immune globulin. Although licensed IVIG preparations contain antivaricella antibodies, the titer of any specific lot of IVIG is uncertain, because IVIG is not tested routinely for antivaricella antibodies. No clinical data demonstrating effectiveness of IVIG for postexposure prophylaxis of varicella are available. The recommended IVIG dose for postexposure prophylaxis of varicella is 1 dose of 400 mg/kg, intravenously (see http://redbook.solutions.aap.org/chapter.aspx?sectionid=88187270&bookid=1484).5Contains only antibody to respiratory syncytial virus.

VACCINATION OF PEOPLE WITH ACUTE ILLNESSES

Every opportunity should be taken to provide needed vaccinations. The decision to delay vaccination because of a current or recent acute illness depends on the severity of the symptoms and their cause. Although a moderate or severe acute illness is sufficient reason to postpone vaccination, minor illnesses (such as diarrhea, mild upper respiratory infection with or without low-grade fever, or other low-grade febrile illness) are not contraindications to vaccination.

People with moderate or severe acute illness, with or without fever, should be vaccinated as soon as the condition improves. This precaution is to avoid superimposing adverse effects from the vaccine on underlying illness, or mistakenly attributing a manifestation of underlying illness to the vaccine. Antimicrobial therapy is not a contraindication to vaccination, with several exceptions:

Antibacterial agents may interfere with the response to oral typhoid vaccine.

Antiviral agents active against herpesviruses (such as acyclovir) may interfere with the response to varicella-containing vaccines.

Antiviral agents active against influenza virus (such as zanamivir and oseltamivir) may interfere with the response to live attenuated influenza vaccine.

Antibiotics may interfere with the response to the new oral cholera vaccine.

A physical examination or temperature measurement is not a prerequisite for vaccinating a person who appears to be in good health. Asking if a person is ill, postponing a vaccination for someone with moderate or severe acute illness, and vaccinating someone who does not have contraindications are appropriate procedures for clinic immunizations.

ALTERED IMMUNOCOMPETENCE

Altered immunocompetence is a general term that is often used interchangeably with the terms immunosuppression, immunodeficiency, and a weakened immune system. It can be caused either by a disease (leukemia, HIV infection) or by drugs or other therapies (cancer chemotherapy, radiation therapy, prolonged high-dose corticosteroids). It can also include conditions such as asplenia and chronic renal disease.

Determination of altered immunocompetence is important because the incidence or severity of some vaccine-preventable diseases is higher in people with altered immunocompetence. Therefore, certain vaccines (such as meningococcal B vaccine, pneumococcal polysaccharide vaccines) are recommended specifically for people with altered immunocompetence. Inactivated vaccines may be safely administered to a person with altered immunocompetence, although response to such vaccines may be suboptimal. These vaccines may need to be repeated after immune function has improved. If immunocompetence does not improve, the usual doses and schedules for inactivated vaccines are recommended. Again, the effectiveness of such vaccinations might be suboptimal.

People with altered immunocompetence may be at increased risk for an adverse reaction after administration of live attenuated vaccines because of reduced ability to mount an effective immune response. Live vaccines should generally be deferred until immune function has improved. If immune function does not improve, live vaccines are contraindicated. This is particularly important when planning to give yellow fever vaccine (see Chapter 3, Yellow Fever). For HIV-infected people with mild or moderate immunosuppression, MMR vaccine is recommended and varicella vaccine can be considered. For an in-depth discussion, see Chapter 8, Immunocompromised Travelers.

VACCINATION SCHEDULING FOR LAST-MINUTE TRAVELERS

As noted, for people anticipating imminent travel, most vaccine products can be given during the same visit. Unless the vaccines given are booster doses of those typically given during childhood, vaccines may require a month or more to induce a sufficient immune response, depending on the vaccine and the number of doses in the series. Some vaccines require more than 1 dose for best protection. Recommended spacing should be maintained between doses (Table 2-05). Doses given at less than minimum intervals may induce lower antibody response than if given according to the recommended schedule. Intervals between doses longer than those routinely recommended do not decrease the immune response when the schedule is completed. Consequently, it is not necessary to restart the series or add doses of any vaccine because of an extended interval between doses, with the exceptions mentioned previously (oral typhoid vaccine and rabies vaccine). If a traveler needs yellow fever vaccination to meet a country requirement under the International Health Regulations, the yellow fever vaccine is not considered valid until 10 days after administration.

Administration of a vaccine earlier than the recommended minimum age or at an interval shorter than the recommended minimum is discouraged. Table 2-05 lists the minimum age and minimum interval between doses for vaccines routinely recommended in the United States.

Because some travelers visit their health care providers at the last minute before departure, studies have been performed to determine whether accelerated scheduling is adequate. This concern is primarily the case for hepatitis B vaccine or the combined hepatitis A and B vaccine. An accelerated schedule for combined hepatitis A and B vaccine has been approved by the Food and Drug Administration (FDA). It is unclear what level of protection any given traveler will have if he or she does not complete a full series of multidose vaccination.

1Adapted from Table 1, CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61.2 Combination vaccines are available. Use of licensed combination vaccines is generally preferred over separate injections of their equivalent component vaccines (CDC. Combination vaccines for childhood immunization. MMWR Recomm Rep. 1999 May 14;48[RR-5]:1–14.). When administering combination vaccines, the minimum age for administration is the oldest age for any of the individual components (exception: the minimum age for the first dose of MenHibrix is 6 weeks); the minimum interval between doses is equal to the largest interval of any of the individual components.3 See www.cdc.gov/vaccines/schedules for recommended revaccination (booster) schedules.4 Combination vaccines containing the HepB component are available (DTaP-HepB-IPV, HepA-HepB). DTaP-HepB-IPV should not be administered to infants aged <6 weeks because of the other components (DTaP, IPV). HepA-HepB is not licensed in the United States for children aged <18 years.5 Calendar months.6 For Hib and PCV, children receiving the first dose of vaccine at ≥7 months of age require fewer doses to complete the series (see the current childhood and adolescent immunization schedule at www.cdc.gov/vaccines).7 If PRP-OMP (Pedvax-Hib, Merck Vaccine Division) was administered at 2 and 4 months of age, a dose at 6 months of age is not indicated. The final dose has a minimum age of 12 months.8 HepB-3 should be administered ≥8 weeks after Hep B-2 and ≥16 weeks after Hep B-1; it should not be administered before age 24 weeks.9 Herpes zoster (shingles) vaccine is recommended as a single dose for people aged ≥60 years.10 Bivalent HPV vaccine is approved for girls/women aged 10–26 years. It is recommended to prevent cervical and other anogenital cancers and precursors for girls/women aged 11–26 years. Quadrivalent HPV and 9vHPV vaccines are approved for boys/men and girls/women aged 9–26 years. They are recommended to prevent cervical and other anogenital cancers, precursors, and genital warts for girls/women aged 11–26 years. They are recommended for boys/men aged 11–21 years and high-risk boys or men (men who have sex with men, HIV-positive men, or immunocompromised men) aged 22–26 years. They may be given to girls aged 9–10 years to prevent the same diseases, and to boys/men aged 9–10 years and 22–26 years to prevent genital warts.11 The third dose of HPV should be administered ≥12 weeks after the second and ≥24 weeks after the first. Dose 3 need not be repeated if administered ≥16 weeks after dose 1, as long as a minimum interval of 4 weeks is maintained between dose 1 and dose 2 and as long as a minimum interval of 12 weeks is maintained between dose 2 and dose 3.12 For people receiving an all-IPV or all-OPV series, if the third dose is given after the fourth birthday, a fourth dose is not needed. For IPV, the next-to-last and the last dose must be spaced by 6 months.13 Two doses of influenza vaccine are recommended for children aged <9 years who are receiving the vaccine for the first time, and for certain incompletely vaccinated children (see reference 2).14 The minimum age for inactivated influenza vaccine varies by vaccine manufacturer. See package insert for vaccine-specific minimum ages.15 Ixiaro is approved by the Food and Drug Administration for people aged ≥2 months.16 Combination MMR-varicella (MMRV) can be used for children aged 12 months through 12 years17 If an infant 6–11 months of age is traveling internationally, a dose of MMR is recommended but does not count toward the 2-dose recommended series. The next dose should be administered at 12–15 months of age and a minimum of 4 weeks from the international travel dose.18Infants aged 2–18 months. Routine vaccination with HibMenCY – TT (MenHibrix) or Menveo (4-dose primary series) is recommended for infants aged 2–18 months who are at increased risk for meningococcal disease. The first dose of either vaccine may be administered as early as age 6 weeks. The fourth dose may be administered as late as age 18 months. Infants and children who received Hib-MenCY-TT and are traveling to areas with high endemic rates of meningococcal disease such as the African “meningitis belt” are not protected against serogroups A and W-135 and should receive a quadrivalent meningococcal vaccination before travel.People aged 9 months through 55 years. People aged 9 months through 55 years at increased risk for meningococcal disease should receive Menveo or Menactra. Infants aged 9–23 months are recommended to receive a 2-dose primary series with a dosing interval of 12 weeks.People aged ≥56 years. Menomune is the only licensed meningococcal vaccine for adults aged ≥56 years and is immunogenic in older adults. For adults who have received a conjugate meningococcal vaccine previously, limited data demonstrate a higher antibody response after a subsequent dose of a conjugate vaccine compared with a subsequent dose of Menomune. For meningococcal vaccine-naïve people aged ≥56 years who anticipate requiring a single dose of meningococcal vaccine (such as travelers and people at risk as a result of a community outbreak), Menomune is preferred. For people now aged ≥56 years who were vaccinated previously with a meningococcal conjugate vaccine and are recommended for revaccination or for whom multiple doses are anticipated (such as people with asplenia and microbiologists), a conjugate vaccine is preferred.19 Revaccination with meningococcal vaccine is recommended for people previously vaccinated who remain at high risk for meningococcal disease. MenACWY is preferred for revaccinating people aged 2–55 years (CDC. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR Recomm Rep. 2013 Mar 22;62[RR-2]:1–28.).20 A second dose of PPSV is recommended for people aged ≥65 years who received a first dose at an age <65 years and at a 5-year minimum interval. A second dose is also recommended for people aged <65 years at highest risk for serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody concentration (CDC. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine [PPSV23]. MMWR Recomm Rep. 2010;59[34]:1102–6.).21 There is no minimum age for preexposure immunization for rabies (CDC. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008 May 23;57[RR-3]:1–28.).22 The first dose of RV must be administered by 14 weeks and 6 days of age. The vaccine series should not be started at ≥15 weeks of age. The final dose in the series should be administered by age 8 months, 0 days. If Rotarix rotavirus vaccine is administered at 2 and 4 months of age, a dose at 6 months of age is not indicated.23 Only 1 dose of Tdap is recommended. Subsequent doses should be given as Td. Children aged 7–10 years who are not fully vaccinated against pertussis and for whom no contraindication to pertussis vaccine exists should receive a single dose of Tdap. If additional doses of tetanus and diphtheria toxoid-containing vaccines are needed, then children aged 7–10 years should be vaccinated according to catch-up guidance, with Tdap preferred as the first dose. Tdap vaccine, when indicated, should be administered regardless of the interval since the last dose of Td vaccine. For management of a tetanus-prone wound, the minimum interval after a previous dose of any tetanus-containing vaccine is 5 years. A dose of Tdap is recommended for pregnant women, preferably at 27–36 weeks’ gestation, regardless of history of previous Tdap vaccination.24 Oral typhoid vaccine is recommended to be administered 1 hour before a meal with a cold or lukewarm drink (temperature not to exceed body temperature—98.6°F [37°C]) on alternate days, for a total of 4 doses.25 The minimum interval from Var-1 to Var-2 for people beginning the series at ≥13 years of age is 4 weeks.26 Yellow fever vaccine may be administered to children aged <9 months in certain situations (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR Recomm Rep. 2010 Jul 30;59[RR-7]:1–27.).

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ALLERGY TO VACCINE COMPONENTS

Vaccine components can cause allergic reactions in some recipients. These reactions can be local or systemic and can include anaphylaxis or anaphylactic-like responses. The vaccine components responsible can include the vaccine antigen, animal proteins, antibiotics, preservatives (such as thimerosal), or stabilizers (such as gelatin). The most common animal protein allergen is egg protein in vaccines prepared by using embryonated chicken eggs (influenza and yellow fever vaccines). People with a history of egg allergy who have experienced only hives after exposure to egg should receive influenza vaccine. Any licensed influenza vaccine that is otherwise appropriate for the recipient’s age and health status may be used.

People who report having had reactions to egg involving symptoms other than hives, such as angioedema, respiratory distress, lightheadedness, or recurrent emesis, or who required epinephrine or another emergency medical intervention, may similarly receive any licensed influenza vaccine that is otherwise appropriate for the recipient’s age and health status. If a person has a severe egg sensitivity or has a positive skin test to yellow fever vaccine but the vaccination is recommended because of their travel destination-specific risk, desensitization can be performed under direct supervision of a physician experienced in the management of anaphylaxis. In such circumstances, both yellow fever and influenza vaccines should be administered in an inpatient or outpatient medical setting. Vaccine administration should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. A previous severe allergic reaction to any vaccine, regardless of the component suspected of being responsible for the reaction, is a contraindication to future receipt of the vaccine.

Some vaccines contain a preservative or trace amounts of antibiotics to which people might be allergic. Providers administering the vaccines should carefully review the prescribing information before deciding if the rare person with such an allergy should receive the vaccine. No recommended vaccine contains penicillin or penicillin derivatives. Some vaccines (MMR vaccine, inactivated polio vaccine [IPV], hepatitis A vaccine, some hepatitis B vaccines, some influenza vaccines, rabies vaccine, varicella vaccine, and smallpox vaccine) contain trace amounts of neomycin or other antibiotics; the amount is less than would normally be used for the skin test to determine hypersensitivity. However, people who have experienced anaphylactic reactions to this antibiotic generally should not receive these vaccines. Most often, neomycin allergy is a contact dermatitis— a manifestation of a delayed-type (cell-mediated) immune response rather than anaphylaxis. A history of delayed-type reactions to neomycin is not a contraindication to receiving these vaccines.

Thimerosal, an organic mercurial compound in use since the 1930s, has been added to certain immunobiologic products as a preservative. Thimerosal is present at preservative concentrations in multidose vials of some brands of vaccine. Receiving thimerosal-containing vaccines has been postulated to lead to induction of allergy. However, there is limited scientific evidence for this assertion. Allergy to thimerosal usually consists of local delayed-type hypersensitivity reactions. Thimerosal elicits positive delayed-type hypersensitivity patch tests in 1%–18% of people tested, but these tests have limited or no clinical relevance. Most people do not experience reactions to thimerosal administered as a component of vaccines, even when patch or intradermal tests for thimerosal indicate hypersensitivity. A localized or delayed-type hypersensitivity reaction to thimerosal is not a contraindication to receipt of a vaccine that contains thimerosal.

Since mid-2001, vaccines routinely recommended for infants have been manufactured without thimerosal as a preservative. Additional information about thimerosal and the thimerosal content of vaccines is available on the FDA website (www.fda.gov/cber/vaccine/thimerosal.htm).

REPORTING ADVERSE EVENTS AFTER IMMUNIZATION

Modern vaccines are extremely safe and effective. Benefits and risks are associated with the use of all immunobiologics—no vaccine is completely effective or completely safe for all recipients. Adverse events after immunization have been reported with all vaccines, ranging from frequent, minor, local reactions to extremely rare, severe, systemic illness, such as that associated with yellow fever vaccine. Adverse events following specific vaccines and toxoids are discussed in detail in each ACIP statement. In the United States, clinicians are required by law to report selected adverse events occurring after vaccination with any vaccine in the recommended childhood series. In addition, CDC strongly recommends that all vaccine adverse events be reported to the Vaccine Adverse Event Reporting System (VAERS), even if a causal relation to vaccination is not certain. VAERS reporting forms and information are available electronically at vaers.hhs.gov, or they may be requested by telephone: 800-822-7967 (toll-free). Clinicians are encouraged to report electronically at https://vaers.hhs.gov/esub/step1.

INJECTION ROUTE AND INJECTION SITE

Injectable vaccines are administered by intramuscular, intradermal, and subcutaneous routes. The method of administration of injectable vaccines depends in part on the presence of an adjuvant in some vaccines. The term adjuvant refers to a vaccine component distinct from the antigen, which enhances the immune response to the antigen. Vaccines containing an adjuvant (DTaP, DT, HPV, Td, Tdap, pneumococcal conjugate, Hib, hepatitis A, hepatitis B) should be injected into a muscle mass, because administration subcutaneously or intradermally can cause local irritation, induration, skin discoloration, inflammation, and granuloma formation. Detailed discussion and recommendations about vaccination of people with bleeding disorders or receiving anticoagulant therapy are available in the ACIP general recommendations on immunization.

Routes of administration are recommended by the manufacturer for each immunobiologic. Deviation from the recommended route of administration may reduce vaccine efficacy or increase local adverse reactions. Detailed recommendations on the route and site for all vaccines have been published in ACIP recommendations; a compiled list of these publications is available on the CDC website at www.cdc.gov/vaccines/hcp/acip-recs (also see Table B-01 in Appendix B).